ABSTRACT ? DEVELOPMENTAL RESEARCH PROGRAM The Developmental Hyperactive Ras Tumor (DHART) SPORE Developmental Research Program (DRP) will support innovative pilot projects to advance the diagnosis and treatment of early stage tumors and advanced cancers characterized by germ line and somatic NF1 mutations. The DRP will accomplish this goal by supporting rigorous translational research in the areas of population science, therapeutics, and mechanisms of disease. We expect that many investigators will utilize DRP support to generate preliminary data leading to successful grant applications to the NIH, the Department of Defense NF Research Program, and other funding agencies, thereby advancing research activities related to NF1-assocated tumors. The translational studies supported by the DRP will also have the potential to replace SPORE projects that have been completed or are not progressing satisfactorily toward achieving their objectives. One objective of the DRP is to fund established investigators who seek to develop a new research theme in the field of NF1-related cancers. This SPORE also includes a Career Development Program (CDP), which is described in a separate section of this application that has the complimentary goal of supporting junior investigators who wish to develop innovative research projects related to the goals of this SPORE. The institutions participating in this application have committed a total of $1.3 million to support the Developmental Programs component of the DHART SPORE (DRP and CDP). Investigators from any of these centers can apply for DRP funds, and we will also consider proposals from researchers at other institutions. The specific aims of the DRP are: (1) To support the development of new techniques and resources to advance translational research to improve the treatment of NF1-associated tumors; (2) to provide funds that will allow investigators to generate pilot feasibility data for grant applications to the NIH or other federal funding agencies; (3) to expand the scope of research in NF1-assocaited tumors with an emphasis on supporting high risk/high reward projects; and (4) to recruit talented investigators into NF1 research as it relates to cancer, and to promote new collaborations in this field through structured interactions with DHART SPORE investigator and assistance from the Administrative, Omics, and Biospecimen/Pathology Cores. The DRP will provide evaluation, funding, and oversight for a minimum of two pilot projects per year, with the potential for a single renewal. Each project will receive a minimum of $50,000 with a maximum of $75,000. Applications for DRP support (including requests for a second year of funding) will be evaluated through a competitive process with review by a Developmental Programs Steering Committee comprised on senor scientists participating in this SPORE and oversight and guidance from the External and Internal Advisory Boards.